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1.  Dual-Phase CT Collateral Score: A Predictor of Clinical Outcome in Patients with Acute Ischemic Stroke 
PLoS ONE  2014;9(9):e107379.
Background and Purpose
The presence of good collaterals on CT angiography (CTA) is a well-known predictor for favorable outcome in acute ischemic stroke. Recently, multiphase CT has been introduced as a more accurate method in assessing collaterals. The aim of this study was to assess the ability of dual-phase CT to evaluate collateral status and predict clinical outcome.
Forty-three patients who underwent both dual-phase CT and transfemoral cerebral angiography (TFCA) for occluded intracranial internal carotid artery (ICA) and/or middle cerebral artery (M1 segment) were recruited from a prospectively collected database. The collateral status on dual-phase CT was graded by using a 4-point scale: grade 0 = no collaterals; 1 = some collaterals with persistence of some defects; 2 = slow but complete collaterals; and 3 = fast and complete collaterals. Univariate and multivariate analysis were performed to define the independent predictors for favorable outcome at 3 months.
Dual-phase CT collateral status (ρ = 0.744) showed higher correlation with TFCA collateral status than CTA collateral status (ρ = 0.596) and substantial interobserver agreement (weighted κ = 0.776). In the univariate analysis, age, history of hypertension, collateral scores on CTA, dual-phase CT, and TFCA, occlusion in intracranial ICA, final infarct volume, and symptomatic hemorrhage were significantly associated with outcome. Among them, only the dual-phase CT collateral score was an independent predictor for favorable outcome (OR = 26.342 (2.788–248.864); P = 0.004) in the multivariate analysis.
The collateral status on dual-phase CT can be a useful predictor for clinical outcome in acute stroke patients, especially when advanced CT techniques are not available in emergent situations.
PMCID: PMC4161414  PMID: 25210853
2.  A New Anti-c-Met Antibody Selected by a Mechanism-Based Dual-Screening Method: Therapeutic Potential in Cancer 
Molecules and Cells  2012;34(6):523-529.
c-Met, the high affinity receptor for hepatocyte growth factor (HGF), is one of the most frequently activated tyrosine kinases in many human cancers and a target for cancer therapy. However, inhibitory targeting of c-Met with antibodies has proven difficult, because most antibodies have intrinsic agonist activity. Therefore, the strategy for reducing the agonism is critical for successful development of cancer therapies based on anti-c-Met antibodies. Here we developed a mechanism-based assay method for rapid screening of anti-c-Met antibodies, involving the determination of Akt phosphorylation and c-Met degradation for agonism and efficacy, respectively. Using the method, we identified an antibody, F46, that binds to human c-Met with high affinity (Kd = 2.56 nM) and specificity, and induces the degradation of c-Met in multiple cancer cells (including MKN45, a gastric cancer cell line) with minimal activation of c-Met signaling. F46 induced c-Met internalization in both HGF-dependent and HGF-independent cells, suggesting that the degradation of c-Met results from antibody-mediated receptor internalization. Further-more, F46 competed with HGF for binding to c-Met, resulting in the inhibition of both HGF-mediated invasion and angiogenesis. Consistently, F46 inhibited the proliferation of MKN45 cells, in which c-Met is constitutively activated in an HGF-independent manner. Xenograft analysis revealed that F46 markedly inhibits the growth of subcutaneously implanted gastric and lung tumors. These results indicate that F46, identified by a novel mechanism-based assay, induces c-Met degradation with minimal agonism, implicating a potential role of F46 in therapy of human cancers.
PMCID: PMC3887825  PMID: 23180291
Akt; anti-c-Met antibody; cancer therapy; c-Met; HGF
3.  A NAC transcription factor and SNI1 cooperatively suppress basal pathogen resistance in Arabidopsis thaliana 
Nucleic Acids Research  2012;40(18):9182-9192.
Transcriptional repression of pathogen defense-related genes is essential for plant growth and development. Several proteins are known to be involved in the transcriptional regulation of plant defense responses. However, mechanisms by which expression of defense-related genes are regulated by repressor proteins are poorly characterized. Here, we describe the in planta function of CBNAC, a calmodulin-regulated NAC transcriptional repressor in Arabidopsis. A T-DNA insertional mutant (cbnac1) displayed enhanced resistance to a virulent strain of the bacterial pathogen Pseudomonas syringae DC3000 (PstDC3000), whereas resistance was reduced in transgenic CBNAC overexpression lines. The observed changes in disease resistance were correlated with alterations in pathogenesis-related protein 1 (PR1) gene expression. CBNAC bound directly to the PR1 promoter. SNI1 (suppressor of nonexpressor of PR genes1, inducible 1) was identified as a CBNAC-binding protein. Basal resistance to PstDC3000 and derepression of PR1 expression was greater in the cbnac1 sni1 double mutant than in either cbnac1 or sni1 mutants. SNI1 enhanced binding of CBNAC to its cognate PR1 promoter element. CBNAC and SNI1 are hypothesized to work as repressor proteins in the cooperative suppression of plant basal defense.
PMCID: PMC3467076  PMID: 22826500
4.  Cytogenetic Characterizations of Central Nervous System Tumors: The First Comprehensive Report from a Single Institution in Korea 
Journal of Korean Medical Science  2009;24(3):453-460.
The World Health Organization (WHO) classification of central nervous system (CNS) tumors incorporates morphology, cytogenetics, molecular genetics, and immunologic markers. Despite the relatively large number of CNS tumors with clonal chromosome abnormalities, only few studies have investigated cytogenetic abnormalities for CNS tumors in Korea. Thus, we investigated 119 CNS tumors by conventional G-banded karyotypes to characterize patterns of chromosomal abnormalities involving various CNS tumors, and 92.4% of them were cultured and karyotyped successfully. Totally, 51.8% of karyotypable CNS tumors showed abnormal cytogenetic results, including neuroepithelial tumors (75.0%), meningeal tumors (71.1%), pituitary adenomas (4.2%), schwannomas (44.4%), and metastatic tumors (100.0%). Glioblastomas had hyperdiploid, complex karyotypes, mainly involving chromosomes Y, 1, 2, 6, 7, 10, 12, 13, and 14. Monosomy 22 was observed in 56.4% of meningiomas. There was a significant increase in the frequencies of karyotypic complexity according to the increase of WHO grade between grades I and II (P=0.0422) or IV (P=0.0101). Abnormal karyotypes were more complex at high-grade tumors, suggesting that the karyotype reflects the biologic nature of the tumor. More detailed cytogenetic and molecular characterizations of CNS tumors contribute to better diagnostic criteria and deeper insights of tumorigenesis, eventually resulting in development of novel therapeutic strategies.
PMCID: PMC2698192  PMID: 19543509
Central Nervous System Neoplasms; Karyotype; WHO Classification; Solid Tumor; Chromosome Abnormality

Results 1-4 (4)